Cumulative evidence from in vitro and animal studies suggests that the enzyme cyclooxygenase-2 (COX-2) is important in the development and progression of lung cancer. Epidemiologic studies evaluating the association between the use of aspirin (an inhibitor of COX-2) and the risk of lung cancer have been conflicting, and no study has been conducted to evaluate non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs). Using pre-recorded drug prescription databases of the Tennessee Medicaid program and North Jutland County of Denmark, we propose to conduct two studies in these populations to examine the effect of NSAID use on the risk of lung cancer. The first is a retrospective cohort study of over 10,000 enrollees of the Tennessee Medicaid Program who were diagnosed with chronic obstructive pulmonary diseases (COPD) during the period of 1980 to 2002. The second is a population-based, retrospective cohort study of over 150,000 users of NSAIDs in the general population of North Jutland County during the period of 1991 to 2002. Within the Danish cohort will be a nested case-control study of 350 cases and 700 controls, in which relevant information will be obtained on over the counter (OTC) analgesic use, as well as cigarette smoking and other potential confounding factors. The two studies proposed here complement each other and provide for an international comparison of NSAIDs as possible lung cancer chemoprevention agents. Because the data on NSAID use have already been collected, the studies will be very cost-efficient. More importantly, the use of pre-recorded pharmacy records minimizes potential errors in exposure assessment and provides a major advantage over existing cohort studies in evaluating the potential chemopreventive effect of NSAIDs. Given the high incidence and mortality of lung cancer and high prevalence of NSAID use, the results from our studies may have important public health implications in lung cancer prevention, and could set the stage for future randomized trials of COX-2 inhibitors in cancer prevention.